Angiogenesis, formation of new blood vessels, occurs in human bodies to restore blood flow to injured tissues. It is controlled by various positive and negative regulatory factors. Excessive blood vessel growth may be triggered by certain pathological conditions, such as cancer, age-related macular degeneration, rheumatoid arthritis, retinopathy, and psoriasis. See Martin et al., Carcinogenesis Advanced Access published May 9, 2003; Soubrane et al., Presse. Med., (2002) 31(27):1282; Gravallese et al., Ann. Rheum. Dis., (2003) 62:100; Lahdenranta et al., PNAS 98(18):10368; Xia et al., Blood, 2003, 102(1):161. As a result of excessive angiogenesis, new blood vessels feed diseased tissues and destroy normal tissues. For example, new vessels allow tumor cells to migrate into the blood circulation system and lodge in other organs.
Angiogenesis occurs via a series of steps, including division and migration of endothelial cells, which form the wall of blood vessels. More than 15 proteins are known to activate endothelial cells' growth and movement, such as angiogenin, epidermal growth factor, estrogen, fibroblast growth factor, interleukin 8, prostaglandins E1 and E2, tumor necrosis factor, vascular endothelium growth factor, and granulocyte colony-stimulating factor.
Angiogenesis can be suppressed by inhibiting any angiogenic stimulus. Compounds that effectively inhibit angiogenesis are candidates for treating angiogenesis-related disorders.